Bimodal Respiratory–Locomotor Neurons in the Neonatal Rat Spinal Cord

Abstract

Neural networks that can generate rhythmic motor output in the absence of sensory feedback, commonly called central pattern generators (CPGs), are involved in many vital functions such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce coordinated motor behavior adapted to environmental constraints and to satisfy the basic needs of an organism. In this context, we recently reported the existence of an ascending excitatory influence from lumbar locomotor CPG circuitry to the medullary respiratory networks that is able to depolarize neurons of the parafacial respiratory group during fictive locomotion and to subsequently induce an increased respiratory rhythmicity (Le Gal et al., 2014b). Here, using an isolated in vitro brainstem-spinal cord preparation from neonatal rat in which the respiratory and the locomotor networks remain intact, we show that during fictive locomotion induced either pharmacologically or by sacrocaudal afferent stimulation, the activity of both thoracolumbar expiratory motoneurons and interneurons is rhythmically modulated with the locomotor activity. Completely absent in spinal inspiratory cells, this rhythmic pattern is highly correlated with the hindlimb ipsilateral flexor activities. Furthermore, silencing brainstem neural circuits by pharmacological manipulation revealed that this locomotor-related drive to expiratory motoneurons is solely dependent on propriospinal pathways. Together these data provide the first evidence in the newborn rat spinal cord for the existence of bimodal respiratory-locomotor motoneurons and interneurons onto which both central efferent expiratory and locomotor drives converge, presumably facilitating the coordination between the rhythmogenic networks responsible for two different motor functions.

Shared Components of Rhythm Generation for Locomotion and Scratching Exist Prior to Motoneurons

“…Vertebrate interneurons that are rhythmically active during multiple rhythms have been found for cat locomotion and scratching ( Geertsen et al, 2011 ; Trejo et al, 2015 ), rat locomotion and respiration ( Le Gal et al, 2016 ), turtle swimming and scratching ( Berkowitz, 2002 , 2005 , 2008 , 2010 ), and tadpole and larval zebrafish swimming and struggling ( Soffe, 1993 ; Li et al, 2007 ; Liao and Fetcho, 2008 ). One limitation of single-neuron recording in large vertebrate networks, however, is that an individual cell’s effect on the network’s output is generally so small that it is hard to demonstrate by selectively activating or silencing the neuron.…”

Role of Propriospinal Neurons in Control of Respiratory Muscles and Recovery of Breathing Following Injury

“…Consequently, propriospinal neurons cannot be distinguished based on location alone. In fact, some propriospinal neurons may perform dual functions in respiration and limb movements (Le Gal et al, 2016). In addition, propriospinal neurons may FIGURE 1 | Roles for propriospinal neurons in control of respiratory muscles.…”

“…In fact, the division between ''locomotor'' and ''respiratory'' circuits might not be as precise as is usually assumed. Bimodal spinal neurons were recently described in a neonatal brainstem spinal cord preparation that were expiratory and also received flexor-related drive via propriospinal pathways (Le Gal et al, 2016). Additional research is needed to investigate the potential overlap between locomotor and respiratory neurons in the spinal cord and brainstem as well as their interconnections, particularly in adult animals.…”

Expanding our horizons: central pattern generation in the context of complex activity sequences

“…Although this coordination may at least partly be due to sensory feedback (Schmidt and Goller, 2016;Suthers et al, 2002), there might also be an overarching CPG that links the two. Similarly, individual CPGs for locomotion and breathing in mammals may be coordinated via synaptic connections that increase respiratory rate at the start of locomotion (before chemosensory feedback changes) and decrease it later (Le Gal et al, 2014Gal et al, , 2016, perhaps constituting a CPG at a higher hierarchical level and a slower time scale than the component CPGs.…”